Intraoperative Imaging Research Articles

Review of Clinically Assessed Molecular Fluorophores for Intraoperative Image Guided Surgery

The term “fluorescence” was first proposed nearly two centuries ago, yet its application in clinical medicine has a relatively brief history coming to the fore in the past decade. Nowadays, as fluorescence is gradually expanding into more medical applications, fluorescence image-guided surgery has become the new arena for this technology. It allows surgical teams to real-time visualize target tissues or anatomies intraoperatively to increase the precision of resection or preserve vital structures during open or laparoscopic surgeries. In this review, we introduce the concept of near-infrared fluorescence guided surgery, discuss the recent and ongoing clinical trials of molecular fluorophores (indocyanine green, 5-aminolevulinic acid, methylene blue, IR-dye 800CW, pafolacianine) and their surgical goals, highlight key chemical and medical factors for imaging agent optimization, deliberate challenges and potential advantages, and propose a framework for integrating this technology into routine surgical care in the near future. The notable clinical achievements of these fluorophores over the past decade strongly indicates that the future of fluorescence in surgery is bright with many more patient benefits to come.

Cutting Edge Microscopic Intraoperative Tissue Assessment for Guidance in Oncologic Surgery: A Systematic Review of the Role of Optical Coherence Tomography.

There is a demand for intraoperative diagnostic support and image guidance in oncological surgery. Novel techniques can provide images similar to histopathological slides within a few minutes. Optical coherence tomography (OCT) and full-field OCT (FF-OCT) provide images with resolution greater than a hundred micrometers without the need for exogenous contrast agents or specimen staining. The aim of this systematic review was to assess the current clinical applications of OCT and dynamic cell imaging (DCI) in oncologic surgery, examining the translation challenges and proposing perspectives for improving future clinical applications. The study adhered to the PRISMA guidelines. PubMed, Google Scholar, and ClinicalTrials.gov were searched up to July 2024. Manuscripts reporting data on OCT and (D)-FF-OCT application in oncologic surgery were included in the qualitative analysis. Thirty-one studies met the inclusion criteria. Most were from the fields of dermatologic (25.8%) and breast cancer (29%) surgery, followed by prostate and bladder (9.6%), ovarian (9.6%), head and neck (6.4%), gastrointestinal (6.4%), hepato-biliary (3.2%), and general surgery (9.6%). The majority of articles focused on FF-OCT and DCI (80.6%). Compared with the gold standard of final pathology, the OCT sensitivity ranged between 66.7 and 94%, the specificity between 64 and 100%, and the accuracy between 73 and 96%. The medical use of OCT has expanded from ophtalmology to other fields including gastroenterology and oncology and, with techniques such as FF-OCT and DCI, can enable rapid intraoperative diagnosis beyond classic histopathology.

Rouvière's Sulcus as a Landmark for a Safe Laparoscopic Cholecystectomy: An Interim Analysis of a Multicenter Cross-sectional Study on the Prevalence and Morphologic Type of Rouvière's Sulcus in the Italian Population.

Laparoscopic cholecystectomy is the gold standard in the treatment of symptomatic gallstones. The large number of gallbladders removed every year is not fully consistent with the excessively high incidence of iatrogenic bile duct injury (IBDI). Several strategies have been suggested to reduce this risk. Among them, the use of extra biliary anatomic structures, such as the Rouvière's sulcus, as a landmark to guide the surgeon during dissection has been proposed as a means to prevent IBDI. The main aim of the present paper is the evaluation of the prevalence of Rouvière's sulcus (RS) and its anatomic variants in a given population. This observational, cross-sectional, and multicenter study has been conducted at the Department of Digestive and Emergency Surgery of the "Azienda Ospedaliera Santa Maria," Terni (Italy), at the Department of Surgical Sciences of the "Azienda Ospedaliera Perugia," Perugia (Italy) and at the Department of Emergency and Trauma Surgery of the "Policlinico Umberto I," Rome (Italy). Intraoperative images of 111 patients undergoing laparoscopic cholecystectomy were analyzed to identify the presence and type of RS, according to the Singh-Prasad classification and the Dahmane classification. RS was present in 93 (83.8%) patients. Singh-Prasad type 1A is present in 48.4% of patients, type 1B in 25.8%, type 2 in 12.9% and type 3 in 12.9%. Dahmane's open type is present in 48.4% of patients and fused type in 51.6%. Due to its high prevalence, RS can be used as an anatomic landmark and probably reduces the incidence of IBDI during laparoscopic cholecystectomy.

Impact of Intraoperative Imaging Techniques on Surgical Margins and Recurrence Rates in Breast-Conserving Surgery

Background: Achieving clear surgical margins is critical in breast-conserving surgery (BCS) to minimize recurrence risk and reduce reoperation rates. Intraoperative imaging techniques provide real-time margin assessment, allowing surgeons to improve surgical precision and outcomes. Objectives: The aim and objectives of this study were to determine the effect of intraoperative imaging on margin clearance, reoperation rates, recurrence as well as the effect of key biomarkers influencing breast cancer including estrogen receptor (ER), progesterone receptor (PR), HER2, Ki67. Methods: 300 patients were divided into two groups, Group-A intraoperative imaging was done in 150 subjects while in Group-B was not done for 150 subjects. The correlation with surgical outcomes (margin status, reoperation rate, and recurrence rate), the biomarker analyzed were expression (ER, PR, HER2, Ki67). Logistic regression, Kaplan-Meier survival analysis whereas p values was performed by using 95% confidence interval (CI). Results: Intraoperative imaging was associated with significantly lower rates of positive margins (15% vs. 25%, p = 0.03), particularly in ER positive and Ki67 low tumors. Both imaging and reoperation rates were reduced (12% vs. 22%, p = 0.02) in the imaging group, in particular for ER positive patients. Reoperation rates were higher in patients with high Ki67 expression (p = 0.01) and recurrence rates were higher in patients with high Ki67 expression (p = 0.03). Kaplan-Meier analysis showed better recurrence-free survival in the imaging group, especially in ER-positive patients (HR: 0.55, p = 0.02). Conclusion: The intraoperative imaging improves margin clearance and reduces reoperation and recurrence for biologically less aggressive tumors (ER positive, low Ki67). Nevertheless, additional therapeutic strategies may be necessary for patients in high-risk subgroups, such as HER2 positive and high Ki67 tumors, to achieve optimal outcomes.

CT-augmented digital tomosynthesis image reconstruction in image-guided bronchoscopy interventions.

Transbronchial needle biopsy is crucial for diagnosing lung cancer, yet its efficacy depends on accurately localizing the target lesion and biopsy needle. Digital tomosynthesis (DTS) is considered a promising imaging modality for guiding bronchoscopy procedures due to its low radiation dose and small footprint relative to cone-beam computed tomography (CBCT). However, the image quality of DTS is still not sufficient for an accurate guidance, mainly due to its limited-angleacquisition. Preoperative computed tomography (CT) scans are often performed prior to bronchoscopy interventions for diagnosis or to plan the procedure. The CT images are of high quality and are characterized by a high spatial resolution compared to intraoperative DTS images. These patient-specific prior CT images and the intraoperative DTS images share a fair amount of anatomical information. The main differences only stem from patient positioning and respiratory motion. When these differences are addressed properly, prior CT images augment intraoperative DTS image reconstruction with strong prior knowledge and potentially enhance DTS imagequality. We propose in this work a prior-aided DTS image reconstruction technique leveraging prior CT images to improve DTS image quality. This technique is based on a recently published deformable CT-to-DTS image registration algorithm which is customized for bronchoscopy interventions. The main idea is to register a prior CT image to an intermediate DTS image reconstructed using the standard iterative algebraic reconstruction technique (ART), then to re-reconstruct the DTS image using ART and the registered prior CT image as a firstestimation. The proposed prior-aided reconstruction method was tested on a physical phantom and six patient bronchoscopy datasets. Real DTS data acquired with a pseudo-linear (PL) scan geometry and simulated DTS data generated according to a spherical ellipse (SE) scan geometry were considered. Results evaluated qualitatively by visual inspection and quantitatively by computing Pearson's correlation (PC) with respect to the reference CBCT images suggest significant improvements in image quality using the prior-aided DTS reconstruction compared to the standard zero-initialized ART reconstruction. PC coefficients of the six patient datasets were on average and using a zero-initialized ART reconstruction with SE data and PL data, respectively, and and using the proposed prior-aided reconstruction with SE data and PL data,respectively. While the initial estimation in iterative reconstruction algorithms is often overlooked, we proved that initial estimation is of critical importance in DTS image reconstruction and we have demonstrated the profound advantages of integrating prior CT images in intraoperative DTS image reconstruction. CT-augmented DTS offers a viable alternative to CBCT in guiding bronchoscopy interventions at a fraction of the radiation dose. Further clinical studies are needed to validate improved diagnosticyield.

Intraoperative Real-Time Near-Infrared Image-Guided Surgery to Identify Necrotic Tissues.

The usefulness of intraoperative real-time fluorescence navigation using indocyanine green (ICG) for metastatic brain tumors, schwannomas, and meningiomas is well established. However, its application in cases of radiation-induced brain necrosis remains unexplored. Surgical intervention is performed in symptomatic and medically refractory cases; however, radiation-necrotic lesions often exhibit a diffuse pattern with unclear surgical boundaries, making it challenging for surgeons to identify the lesion during the surgery. Four patients with intracranial necrotic tissues received 1.5 mg/kg ICG 1 hour before observation during the surgery. We used near-infrared fluorescence to identify the necrotic location. Case 1: A 61-year-old man with lung cancer and metastatic brain tumor history exhibited left-sided weakness a year after craniotomy and radiotherapy. A new lesion required surgery, where ICG fluorescence imaging highlighted a significant contrast in the resection cavity, aiding in successful lesion removal without complications. Case 2: A 51-year-old man with resected glioblastoma developed paralysis. ICG fluorescence during surgery confirmed necrosis and enabled the lesion's removal despite potential inaccuracies due to brain shift, without ICG-related complications. Near-infrared fluorescence could visualize necrotic tissues in all 4 cases. The mean signal-to-background ratio of the necrotic tissues in delayed window ICG was 3.5 ± 0.7. The ratio of the gadolinium-enhanced T1 tumor signal to the brain (T1-weighted background ratio) was 2.3 ± 0.4. This report is the first to demonstrate the efficacy of ICG intraoperative fluorescence imaging in identifying radiation-induced necrotic brain tissues.

Digital instrument simulator to optimize the development of hyperspectral systems: application for intraoperative functional brain mapping.

Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. These areas can be assessed by monitoring cerebral hemodynamics and metabolism. Robust quantification of these biomarkers is complicated to perform during neurosurgery due to the critical context of the operating room. In actual devices, the inhomogeneities of the optical properties of the exposed brain cortex are poorly taken into consideration, which introduce quantification errors of biomarkers of brain functionality. Moreover, the best choice of spectral configuration is still based on an empirical approach. We propose a digital instrument simulator to optimize the development of hyperspectral systems for intraoperative brain mapping studies. This simulator can provide realistic modeling of the cerebral cortex and the identification of the optimal wavelengths to monitor cerebral hemodynamics (oxygenated and deoxygenated hemoglobin Hb) and metabolism (oxidized state of cytochromes and and cytochrome-c-oxidase oxCytb, oxCytc, and oxCCO). The digital instrument simulator is computed with white Monte Carlo simulations of a volume created from a real image of exposed cortex. We developed an optimization procedure based on a genetic algorithm to identify the best wavelength combinations in the visible and near-infrared range to quantify concentration changes in , Hb, oxCCO, and the oxidized state of cytochrome and (oxCytb and oxCytc). The digital instrument allows the modeling of intensity maps collected by a camera sensor as well as images of path length to take into account the inhomogeneities of the optical properties. The optimization procedure helps to identify the best wavelength combination of 18 wavelengths that reduces the quantification errors in , Hb, and oxCCO by 47%, 57%, and 57%, respectively, compared with the gold standard of 121 wavelengths between 780 and 900nm. The optimization procedure does not help to resolve changes in cytochrome and in a significant way but helps to better resolve oxCCO changes. We proposed a digital instrument simulator to optimize the development of hyperspectral systems for intraoperative brain mapping studies. This digital instrument simulator and this optimization framework could be used to optimize the design of hyperspectral imaging devices.

Accuracy of cervical pedicle screw placement with a robotic guidance system via the open midline approach.

An increasing number of studies have shown that a robotic guidance system (RGS) can provide accurate cervical pedicle screw (CPS) placement. The accuracy of CPS placement with an RGS has mostly been evaluated according to the magnitude of pedicular cortical violation. However, an RGS assists in pedicle screw (PS) placement by directly indicating the preplanned trajectory in the operative field. Therefore, investigating how accurately the planned trajectory is executed is essential to determine the accuracy of CPS placement using an RGS, in addition to evaluating the clinical accuracy. Hence, this study aimed to evaluate the accuracy of CPS placement using an RGS by comparing the executed trajectory with the planned trajectory. This prospective study analyzed 174 CPSs placed between C2 and C6 in 39 consecutive patients who underwent cervical fusion surgery using an RGS. The deviation of the executed CPS trajectory from the planned trajectory was measured at the entry point and at a depth of 20 mm in both the axial and sagittal planes on CT images. Additionally, its direction was noted (lateral or medial in the axial plane and cephalad or caudal in the sagittal plane). These measurements were analyzed according to spinal levels (C2 and C3-C6), laterality (right and left sides), and registration material (preoperative and intraoperative CT images). Furthermore, clinical accuracy was assessed using the Neo classification (grades 0-3). Overall, the mean (± SD) deviations from the planned trajectory at the entry point and at a depth of 20 mm were 0.79 ± 0.65 mm and 0.86 ± 0.69 mm in the axial plane and 0.88 ± 0.81 mm and 0.82 ± 0.79 mm in the sagittal plane, respectively. When separately examining the deviations according to spinal level, laterality, and registration material, the mean deviations were < 1 mm at any point. Analysis of the deviation direction showed that the CPSs were placed divergently from the planned trajectory in the axial plane. In the sagittal plane, the CPSs were likely to be inserted parallel to the planned trajectory. However, at C2 the CPSs were placed in the caudal direction relative to the planned trajectory. Regarding clinical accuracy, the acceptable rates (grades 0 and 1) were 97.7% and 97.1% in the axial and sagittal planes, respectively, without any CPS-related complications. This study suggests that an RGS can reliably execute planned trajectories, aiding accurate CPS placement in clinical settings.

Image fusion for intraoperative evaluation of microwave ablation in non-small cell lung cancer: a retrospective cohort study.

Patients with early-stage non-small cell lung cancer (NSCLC) who are intolerant to surgery have a poor prognosis. Microwave ablation is an effective treatment method. However, the density of the lesion may occasionally be similar to that of the ablation zone, thus rendering it difficult to identify the relative position of the lesion and ablation zone during ablation. This study aimed to use image fusion technology to help confirm the relative position of lesions and ablation zones and to facilitate immediate assessment of the residual lesions. This retrospective study was conducted in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, between August 2019 and August 2021, and consecutively included patients who had undergone computed tomography (CT)-guided percutaneous microwave ablation for NSCLC. A single radiologist manually fused the intraoperative CT images alignment of the lesions. Two other clinicians examined the postoperative CT images and the fused CT images to determine whether a lesion remained and to measure the minimum ablative margin (MAM). One of the clinicians assessed the complete ablation rate on CT images 6 months after ablation. The Chi-squared test was used to calculate the kappa coefficients between the two investigators. Binary logistic regression was used to analyze the correlation between each characteristic parameter of the lesion and image quality. The clinicians involved in this study all had over 10 years of work experience. Among the 29 participants, comprising 32 lesions retrospectively included (median age 65 years; 41.4% male), the image fusion success rate was 96.88%, and the median fusion time was10 minutes. The rate of accurate recognition for the relative position of pulmonary nodules and ablation zone on original CT images of the two physicians was 7.52% and 12.90%, respectively, while that achieved from the fused CT images was 87.1% and 86.0%, respectively; in agreement testing, the kappa coefficient between the physicians was 0.859 (P<0.001). The MAM on fused images was 3.05±1.35 mm (range, 1.1-6.7 mm). The quality of fused images was positively correlated with the CT values of focus (P=0.009). The complete ablation rate (93.5%) indicated by immediate image fusion post ablation was consistent with that determined by CT images after 6 months after ablation, with 100% sensitivity and specificity. Image fusion is a valuable strategy for evaluating whether intraoperative ground glass nodules are completely ablated by microwave ablation.

Integration of a lightweight and table-mounted robotic alignment tool with automated patient-to-image registration using robotic cone-beam CT for intracranial biopsies and stereotactic electroencephalography.

Robotics in neurosurgery is becoming increasingly prevalent. The integration of intraoperative imaging for patient registration into workflows of newer robotic systems enhances precision and has further driven their widespread adoption. In this study, the authors report on a lightweight, table-mounted robotic system integrating robotic cone-beam CT (CB-CT) for automated patient registration in cranial biopsies and stereotactic electroencephalography (sEEG). This prospective cohort study included patients who underwent stereotactic biopsy or sEEG with the Cirq system from January 2023 to August 2024. For patient-to-image registration, an external registration matrix was secured near the patient's head before conducting CB-CT with robotic Artis Pheno. CT was then fused with preoperative planning MRI and used as the navigation dataset. Demographic and clinical data were evaluated, and entry and target errors, as well as vector deviation of sEEG electrodes, were assessed and compared with those of patients who underwent biopsies and sEEG with the frameless VarioGuide system. In 26 Cirq-assisted surgical procedures, robotic CB-CT was used for image registration in 20 cases. Of these, 15 were biopsies (mean ± SD 7 ± 1 specimens) and 5 were sEEG with 31 depth electrodes, compared to 29 VarioGuide biopsies and 3 VarioGuide sEEG cases with 25 electrodes. The mean age was 56 ± 19 years, with a male/female ratio of 1.9:1. Lesion size averaged 19 ± 17 cm3 on T1-weighted imaging and 61 ± 53 cm3 on T2-weighted imaging for Cirq and 14 ± 14 cm3 and 68 ± 47 cm3 for VarioGuide. The mean surgical times were 117 ± 34 minutes for biopsy and 269 ± 54 minutes for sEEG in the Cirq group, with skin-to-skin times of 40 ± 23 minutes for biopsy and 208 ± 74 minutes for sEEG; in comparison, surgical times of 78 ± 21 minutes for biopsy and 218 ± 33 minutes for sEEG were reported with VarioGuide, with skin-to-skin times of 34 ± 13 and 158 ± 27 minutes. No complications occurred. The mean dosage area product was 983 ± 351 µGym2 for biopsies and 1772 ± 968 µGym2 for sEEG. Cirq-assisted sEEG electrodes had mean entry and target errors of 1.4 ± 1.2 mm and 2.6 ± 1.6 mm, compared to 5.3 ± 3.3 mm and 6.5 ± 2.8 mm with VarioGuide. Mean vector deviation was 1.6 ± 0.9 mm with Cirq versus 4.9 ± 2.9 mm with VarioGuide. The integration of a lightweight, table-mounted robotic alignment tool with intraoperative CB-CT for automated patient-to-image registration enables high precision and a seamless workflow. This combination is safe, has a manageable learning curve, and holds potential to replace traditional frame-based and frameless procedures. Its efficiency and accuracy are likely to contribute to the increasing adoption of robotics in neurosurgery.

Sensitivity and Costs of Intraoperative Trans-Impedance Matrix Recordings, Spread of Excitation Functions, and X-ray Imaging in Detecting Cochlear Implant Tip Foldovers.

Evaluate the sensitivity and financial costs of Trans-Impedance Matrix recordings, Spread of Excitation functions, and x-rays in detecting cochlear implant tip foldovers. Tertiary academic medical center. 113 ears of 108 patients. Following cochlear implantation and before concluding surgery, intraoperative Trans-Impedance Matrix recordings, Spread of Excitation functions, and x-rays were conducted to evaluate presence of tip foldover. Presence of tip foldover; recording time necessary for and costs of Trans-Impedance Matrix, spread of excitation, and x-rays. There were six tip foldovers. Trans-Impedance Matrix showed 100% sensitivity, 100% specificity, 100% positive predictive value, and 100% negative predicative value in detecting tip foldovers. Spread of excitation showed 29% sensitivity, 99% specificity, 67% positive predictive value, and 95% negative predicative value. Trans-Impedance Matrix recordings were completed significantly faster than spread of excitation and x-rays. Elimination of x-rays from our intraoperative workflow results in a twofold cost reduction. Trans-Impedance Matrix recordings have potential great clinical utility in evaluating proper CI placement intraoperatively and reducing costs of surgery while not compromising patient care. Given the low tip foldover rate, a multicenter study is in progress to evaluate the sensitivity, specificity, positive predictive value, and negative predicative value of Trans-Impedance Matrix in a larger dataset. This can provide better guidance to cochlear implant clinics interested in evaluating the impact of using Trans-Impedance Matrix on patient care as well as the economics of reducing use of intraoperative imaging.

Exploring the use of the mobile PET/CT-camera for intraoperative imaging of surgical specimens of the (para)thyroid and/or cervical lymph nodes V. Vergucht, B. Lambert

exploring the use of the mobile PET/CT-camera for intraoperative imaging of surgical specimens of the (para)thyroid and/or cervical lymph nodes V. Vergucht, B. Lambert

Subthalamic Deep Brain Stimulation under General Anaesthesia for Parkinson's Disease: Institutional Experience and Outcomes.

Direct targeting in deep brain stimulation (DBS) has remarkably impacted the patient's experience throughout the surgery and the overall logistics of the procedure. When the individualised plan is co-registered with a 3D image acquired intraoperatively, the electrodes can be safely placed under general anaesthesia. How this applies to a general practice scenery (outside clinical trials and in a moderate caseload centre) has been scarcely reported. Prospective single-centre study of patients treated with asleep subthalamic DBS for Parkinson's disease between January 2021 and December 2022. Clinical, motor, medication-dependence and quality-of-life outcomes were evaluated after optimal programming (6 months). Wilcoxon test was used to compare pre- versus post-repeated measures. Surgical-related parameters were also analysed. 89 patients primarily operated for DBS were included in the study. Intraoperative electrode replacement was not necessary. Mean surgical duration was 217 (SD 44) minutes, including the implantation of the generator; and mean length of stay was 3 (SD 1) days. There was one surgical-related complication (delayed infection). Significant and clinically relevant improvement was seen in UPRS III (mean decrease 62%) (p<0.001) and PDQ-8 (50% increase) (p<0.001) after 6 months. Daily doses of medication were decreased by a mean of 68%, p<0.001). DBS can be safely performed under general anaesthesia in a pragmatic clinical environment, provided a multidisciplinary committee for patient selection and a dedicated surgical and anaesthetic team are available. The effectiveness in ameliorating motor symptoms, the ability to reduce the drug load, and the improvement in quality of life demonstrated in clinical trials could be reproduced under more generalised conditions as in our centre. The need for a team learning curve and the progressive evolution in, and adaptation to, trajectory planning software, anaesthetic management, intraoperative imaging, DBS device upgrades and programming schemes should be contemplated in the transition process to direct targeting.

Glutathione-activated near-infrared II fluorescent probe for lung metastatic diagnosis and intraoperative imaging of tumor

Accurate identification of intraoperative tumor lesions and effective treatment are crucial for improving surgical outcomes. Near-infrared (NIR) fluorescence imaging demonstrates advantages over traditional medical approaches in tumor interventions, garnering significant attention. However, clinically available imaging agents are generally limited by their "always on" characteristics, which can lead to non-specific imaging interference and "false-positive" results. In this context, we present a glutathione-activated NIR-II probe, LJ-GSH, designed for metastatic tumor imaging and specific imaging-guided tumor resection. LJ-GSH initially exhibits quenched fluorescence due to the weak electron-donating effect of the thiophenol moiety, which is recovered at 815/910 nm upon activation by the overexpressed levels of glutathione (GSH) in tumor cells and tissues, significantly enhancing the specificity of tumor imaging. This unique characteristic positions LJ-GSH as a reliable fluorescent sensor for monitoring GSH dynamics during physiological events. Notably, the probe's NIR-II emission feature markedly improves imaging contrast and resolution, facilitating real-time identification and imaging of lung metastatic lesions. With the aid of high-specific NIR-II imaging guidance, tumor tissues can be precisely resected, with the residual negative margin diameter reduced to approximately 0.2 mm. We envision that our tailored probe may offer an attractive option for clinical applications.

A Tandem-Locked Fluorescent Probe Activated by Hypoxia and a Viscous Environment for Precise Intraoperative Imaging of Tumor and Instant Assessment of Ferroptosis-Mediated Therapy.

Noninvasive fluorescence detection of tumor-associated biomarker dynamics provides immediate insights into tumor biology, which are essential for assessing the efficacy of therapeutic interventions, adapting treatment strategies, and achieving personalized diagnosis and therapy evaluation. However, due to the absence of a single biomarker that effectively reflects tumor development and progression, the currently available optical diagnostic agents that rely on "always-on" or single pathological activation frequently show nonspecific fluorescence responses and limited tumor accumulation, which inevitably compromises the accuracy and reliability of tumor imaging. Herein, based on intramolecular charge transfer (ICT) and twisted intramolecular charge-transfer (TICT) hybrid mechanisms, we report a tandem-locked probe, NTVI-Biotin, for simultaneously specific imaging-guided tumor resection and ferroptosis-mediated tumor ablation evaluation under the coactivation of nitro reductase (NTR)/viscosity. The dual-stimulus-responsive design strategy ensures that NTVI-Biotin exclusively activates near-infrared (NIR) fluorescence signals upon interaction with both NTR and elevated viscosity levels through triggering ICT on while inhibiting the TICT process. Meanwhile, functionalization with a tumor-targeting hydrophilic biotin-poly(ethylene glycol) moiety enhances tumor accumulation. The probe's dual-response and tumor-targeting design minimizes nonspecific tissue activation, allowing for precise tumor identification and lesion removal with a superior tumor-to-normal tissue (T/N > 6) ratio. More importantly, NTVI-Biotin was capable of evaluating ferroptosis-mediated chemotherapeutics by real-time monitoring of the alternations of NTR/viscosity levels. The results reveal that the increased tumor signals of NTVI-Biotin following the combination of ferroptosis and chemotherapy correlate well with the tumor growth inhibition, demonstrating the potential of NTVI-Biotin to assess therapeutic efficacy.

Clinical Evaluation of the NaviNetics Stereotactic System Using Intraoperative Portable Surgical Imaging System in DBS Surgery

BACKGROUND AND OBJECTIVES: A typical workflow for deep brain stimulation (DBS) surgery consists of head frame placement, followed by stereotactic computed tomography (CT) or MRI before surgical implantation of the hardware. At some institutions, this workflow is prolonged when the imaging scanner is located far away from the operating room, thereby increasing workflow times by the addition of transport times. Recently, the intraoperative O-arm has been shown to provide accurate image fusion with preoperative CT or MR imaging, suggesting the possibility of obtaining an intraoperative localization scan and postoperative confirmation. In this article, we aim to evaluate the compatibility of the stereotactic frame system with the intraoperative O-arm system regarding lead accuracy and surgical flow. METHODS: A total of 17 patients undergoing DBS surgery for movement disorders were evaluated. One patient underwent both the stereotactic CT and O-arm localization, while 16 patients underwent only intraoperative O-arm localization. Following lead placement, intraoperative O-arm imaging was obtained to evaluate the accuracy of the lead placement. Accuracy was defined as the error measured as the distance from the center of the planned trajectory to the cannula. RESULTS: Less than 0.1 mm difference was found between the O-arm imaging technique and CT image localization of the NaviNetics stereotactic head frame in DBS surgery. Of the 16 patients who underwent the intraoperative O-arm imaging alone, the targets included bilateral ventral intermediate nucleus (16 leads), bilateral globus pallidus internus (4 leads), and subthalamic nucleus (12 leads). The mean ± SD radial error in the probe's eye view was 0.71 ± 0.33 mm for n = 32 leads. No tract hemorrhage was observed. CONCLUSION: Intraoperative O-arm imaging can be used safely and effectively for stereotactic registration and lead placement confirmation with the stereotactic system in both awake and asleep DBS surgery.

Automatic Image Registration Provides Superior Accuracy Compared with Surface Matching in Cranial Navigation.

The precision of neuronavigation systems relies on the correct registration of the patient's position in space and aligning it with radiological 3D imaging data. Registration is usually performed by the acquisition of anatomical landmarks or surface matching based on facial features. Another possibility is automatic image registration using intraoperative imaging. This could provide better accuracy, especially in rotated or prone positions where the other methods may be difficult to perform. The aim of this study was to validate automatic image registration (AIR) using intraoperative cone-beam computed tomography (CBCT) for cranial neurosurgical procedures and compare the registration accuracy to the traditional surface matching (SM) registration method based on preoperative MRI. The preservation of navigation accuracy throughout the surgery was also investigated. Adult patients undergoing intracranial tumor surgery were enrolled after consent. A standard SM registration was performed, and reference points were acquired. An AIR was then performed, and the same reference points were acquired again. Accuracy was calculated based on the referenced and acquired coordinates of the points for each registration method. The reference points were acquired before and after draping and at the end of the procedure to assess the persistency of accuracy. In total, 22 patients were included. The mean accuracy was 6.6 ± 3.1 mm for SM registration and 1.0 ± 0.3 mm for AIR. The AIR was superior to the SM registration (p < 0.0001), with a mean improvement in accuracy of 5.58 mm (3.71-7.44 mm 99% CI). The mean accuracy for the AIR registration pre-drape was 1.0 ± 0.3 mm. The corresponding accuracies post-drape and post-resection were 2.9 ± 4.6 mm and 4.1 ± 4.9 mm, respectively. Although a loss of accuracy was identified between the preoperative and end-of-procedure measurements, there was no statistically significant decline during surgery. AIR for cranial neuronavigation consistently delivered greater accuracy than SM and should be considered the new gold standard for patient registration in cranial neuronavigation. If intraoperative imaging is a limited resource, AIR should be prioritized in rotated or prone position procedures, where the benefits are the greatest.

Intraoperative Detection of Screw Penetration Following Volar Plating of the Distal Radius: A Cadaveric Study Comparing Fluoroscopic Imaging and Ultrasound

Abstract Introduction Hardware prominence is one of the major established complications following volar plating of distal radius fractures. The purpose of this cadaveric study is to compare two conventional fluoroscopic imaging views (carpal shoot-through view [CSV] and dorsal horizon view [DHV]) with ultrasound (US) to establish the best intraoperative imaging modality for surgeons to use to identify penetration of screws through the dorsal cortex and/or into the distal radioulnar joint (DRUJ). Materials and Methods Twelve human cadaveric limbs were included in the study, instrumented with distal radius plates via a volar approach. The three imaging modalities, CSV, DHV, and US, were compared in terms of detecting prominent screws during volar plate fixation. Six surgeons with varying levels of expertise performed the evaluations. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and the area under the receiver operating characteristic curve were computed for every surgeon and imaging method. Results The CSV was found to be more sensitive compared with the DHV and US for detecting dorsal cortex penetration (99% vs. 94% vs. 56%, respectively). The DHV was found to be more sensitive in recognizing DRUJ screw penetration compared with CSV and US (89% vs. 78% vs. 11%, respectively). US evaluation demonstrated considerably lower diagnostic utility compared with CSV and DHV. Surgeon's ability to perform as well as confidence in evaluating for screw penetration was highest with the CSV view. Conclusion Fluoroscopic imaging, particularly the CSV, demonstrates greater diagnostic reliability compared with US for intraoperative detection of prominent screws following volar plate fixation of the distal radius. CSV was also identified as the most reproducible examination for all levels of expertise with minimal formal training required. Level of Evidence: Therapeutic level V.

Real-time intraoperative ultrasound imaging of the posterior pituitary gland during endoscopic endonasal approach.

Pituitary adenomas are amongst the most common benign central nervous system tumors, and often require resection via an endoscopic endonasal approach (EEA). Two of the most common associated complications are central diabetes insipidus (DI) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Both are thought to be caused by manipulation of the posterior pituitary gland (PPG), making intraoperative visualization and preservation of this structure critical. Intraoperative endoscopic endonasal ultrasound (IEUS) may present an optimal tool for this purpose. This study aims to describe the appearance and morphology of the PPG on IEUS. This study included all pituitary adenoma surgeries during which IEUS was utilized and the PPG was visualized between 1/1/2022, and 12/31/2023. Demographic, clinical, pathological, and radiological data were retrospectively collected. The PPG was described as either hypoechoic, isoechoic, or hyperechoic as compared to the anterior pituitary gland and adenoma, and the morphology of the PPG was further classified as ellipse or crescent shaped. The PPG was hypoechoic in all 43 cases included in our final cohort (100.0%). Morphologically, the PPG appeared elliptical in 27 cases (62.8%), and crescent shaped in 16 cases (37.2%). The PPG can typically be visualized by IEUS as a hypoechoic structure immediately anterior to the posterior wall of the sella turcica, with elliptical morphology being the most common appearance. These characteristics can be used by the skull base surgeon to more confidently identify the position and morphology of the PPG intraoperatively for its' preservation.

Selecting Targets for Molecular Imaging of Gastric Cancer: An Immunohistochemical Evaluation.

Tumor-targeted positron emission tomography (PET) and fluorescence-guided surgery (FGS) could address current challenges in pre- and intraoperative imaging of gastric cancer. Adequate selection of molecular imaging targets remains crucial for successful tumor visualization. This study evaluated the potential of integrin αvβ6, carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5), epidermal growth factor receptor (EGFR), epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor-2 (HER2) for molecular imaging of primary gastric cancer, as well as lymph node and distant metastases. Expression of αvβ6, CEACAM5, EGFR, EpCAM and HER2 was determined using immunohistochemistry in human tissue specimens of primary gastric adenocarcinoma, healthy surrounding stomach, esophageal and duodenal tissue, tumor-positive and tumor-negative lymph nodes, and distant metastases, followed by quantification using the total immunostaining score (TIS). Positive biomarker expression in primary gastric tumors was observed in 86% for αvβ6, 72% for CEACAM5, 77% for EGFR, 93% for EpCAM and 71% for HER2. Tumor expression of CEACAM5, EGFR and EpCAM was higher compared to healthy stomach tissue expression, while this was not the case for αvβ6 and HER2. Tumor-positive lymph nodes could be distinguished from tumor-negative lymph nodes, with accuracy ranging from 82 to 93% between biomarkers. CEACAM5, EGFR and EpCAM were abundantly expressed on distant metastases, with expression in 88-95% of tissue specimens. Our findings show that CEACAM5, EGFR and EpCAM are promising targets for molecular imaging of primary gastric cancer, as well as visualization of both lymph node and distant metastases. Further clinical evaluation of PET and FGS tracers targeting these antigens is warranted.